rs4491689

Variant names:

• chr2-26417913-G-A
• rs4491689
• NM_145038.5:c.244-3375G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145038.5(DRC1):​c.244-3375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,206 control chromosomes in the GnomAD database, including 59,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (59108 hom., cov: 31)
• Consequence: DRC1 NM_145038.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 5 publications found

Genes affected

DRC1 (HGNC:24245): (dynein regulatory complex subunit 1) This gene encodes a central component of the nexin-dynein complex (N-DRC), which regulates the assembly of ciliary dynein. Mutations in this gene can cause ciliary dyskinesia. [provided by RefSeq, Aug 2015]

DRC1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 21

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 80

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC1	NM_145038.5	c.244-3375G>A		intron_variant	Intron 2 of 16	ENST00000288710.7	NP_659475.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRC1	ENST00000288710.7	c.244-3375G>A		intron_variant	Intron 2 of 16	2	NM_145038.5	ENSP00000288710.2
DRC1	ENST00000421869.5	n.244-3375G>A		intron_variant	Intron 2 of 7	1		ENSP00000414375.1
DRC1	ENST00000649059.1	n.229-3375G>A		intron_variant	Intron 2 of 15			ENSP00000497543.1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132731 AN: 152086 Hom.: 59071 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.869

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.873 AC: 132825 AN: 152206 Hom.: 59108 Cov.: 31 AF XY: 0.867 AC XY: 64525 AN XY: 74430

African (AFR) AF: 0.888 AC: 36880 AN: 41518

American (AMR) AF: 0.747 AC: 11417 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3032 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1774 AN: 5156

South Asian (SAS) AF: 0.794 AC: 3829 AN: 4824

European-Finnish (FIN) AF: 0.949 AC: 10072 AN: 10610

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62888 AN: 68030

Other (OTH) AF: 0.869 AC: 1839 AN: 2116

Alfa AF: 0.903 Hom.: 195528

Bravo AF: 0.854

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.40
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4491689; hg19: chr2-26640781;